Trial Outcomes & Findings for Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor (NCT NCT02500550)
NCT ID: NCT02500550
Last Updated: 2021-05-18
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
180 days post HSCT
Results posted on
2021-05-18
Participant Flow
Participant milestones
| Measure |
ATIR101
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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|---|---|
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Overall Study
STARTED
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15
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Overall Study
COMPLETED
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8
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Overall Study
NOT COMPLETED
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7
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Reasons for withdrawal
| Measure |
ATIR101
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Overall Study
Death
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7
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Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Age, Continuous
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41 years
n=15 Participants
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|
Sex: Female, Male
Female
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10 Participants
n=15 Participants
|
|
Sex: Female, Male
Male
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5 Participants
n=15 Participants
|
|
Region of Enrollment
Canada
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7 Participants
n=15 Participants
|
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Region of Enrollment
Belgium
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5 Participants
n=15 Participants
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Region of Enrollment
United Kingdom
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2 Participants
n=15 Participants
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Region of Enrollment
Germany
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1 Participants
n=15 Participants
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PRIMARY outcome
Timeframe: 180 days post HSCTPopulation: The primary study endpoint, grade III/IV acute GVHD within 180 days after HSCT, was met for two patients treated with two doses of ATIR101. Two patients developed grade III/IV acute GVHD within 180 days after HSCT treated with a single dose of ATIR101.
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Single dose of ATIR101, grade III/IV acute GVHD within 180 days after HSCT
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2 participants
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Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Two doses of ATIR101, Grade III/IV acute GVHD within 180 days after HSCT
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2 participants
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SECONDARY outcome
Timeframe: Between 6 and 12 months after HSCTPopulation: 7 patients in the single dose and 4 patients in the double dose were analysed to make a total of 11 patients analysed.
Outcome measures
| Measure |
ATIR101
n=11 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Incidence and Severity of Acute and Chronic GVHD
Single dose group acute GVHD between 6 and 12 months after HSCT
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0 Participants
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Incidence and Severity of Acute and Chronic GVHD
Double dose group acute GVHD between 6 and 12 months after HSCT
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0 Participants
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Incidence and Severity of Acute and Chronic GVHD
Single dose group chronic GVHD between 6 and 12 months after HSCT
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0 Participants
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Incidence and Severity of Acute and Chronic GVHD
Double dose group chronic GVHD between 6 and 12 months after HSCT
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2 Participants
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SECONDARY outcome
Timeframe: 6 and 12 months post HSCTPopulation: Cumulative incidence estimates of T-cell reconstitution at 6 and 12 months post HSCT were analyzed for the single dose group (N=9) and double dose group (N=6).
Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Single dose group.
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44.4 percentage of participants
Interval 11.0 to 74.2
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Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Double dose group.
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50.0 percentage of participants
Interval 8.2 to 82.6
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Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Single dose group.
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77.8 percentage of participants
Interval 32.7 to 94.5
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Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Double dose group.
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50.0 percentage of participants
Interval 8.2 to 82.6
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SECONDARY outcome
Timeframe: From 6 months to 1 year after HSCTInfection was defined as (1) a clinically apparent infectious disease with symptoms or (2) a viral reactivation. Severity was graded according to CTCAE vs. 4.0
Outcome measures
| Measure |
ATIR101
n=11 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Viral, Fungal, and Bacterial Infections
Any infection
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10 Participants
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Viral, Fungal, and Bacterial Infections
Severity, grade 1-2
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7 Participants
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Viral, Fungal, and Bacterial Infections
Severity, grade 3-5
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3 Participants
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SECONDARY outcome
Timeframe: 12 months post HSCTPopulation: Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101
Defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Transplant-related Mortality (TRM)
Single-dose group, cumulative estimates of TRM
|
22.2 percentage of participants that died
Interval 2.8 to 53.3
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Transplant-related Mortality (TRM)
Double-dose group, cumulative estimates of TRM
|
66.7 percentage of participants that died
Interval 12.2 to 92.5
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SECONDARY outcome
Timeframe: 12 months post HSCTPopulation: Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101
Defined as death due to disease relapse or disease progression
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Relapse-related Mortality (RRM)
Single dose group, cumulative estimates of RRM 12 months post HSCT
|
11.1 percentage of participants
Interval 0.5 to 40.9
|
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Relapse-related Mortality (RRM)
Double dose group, cumulative estimates of RRM 12 months post HSCT
|
0 percentage of participants
Interval 0.0 to 0.0
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SECONDARY outcome
Timeframe: 12 months post HSCTPopulation: Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101
Defined as the time from HSCT until death from any cause
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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Overall Survival (OS)
Single dose group, Kaplan-Meier estimates of OS 12 months post HSCT
|
66.7 Percentage of participants
Interval 28.2 to 87.8
|
|
Overall Survival (OS)
Double dose group, Kaplan-Meier estimates of OS 12 months post HSCT
|
33.3 Percentage of participants
Interval 4.6 to 67.6
|
SECONDARY outcome
Timeframe: 12 months post HSCTPopulation: Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101
Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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|---|---|
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Progression-free Survival (PFS)
Single dose group, Kaplan-Meier estimates of PFS 12 months post HSCT
|
55.6 Percentage of participants
Interval 20.4 to 80.5
|
|
Progression-free Survival (PFS)
Double dose group, Kaplan-Meier estimates of PFS 12 months post HSCT
|
33.3 Percentage of participants
Interval 4.6 to 67.6
|
SECONDARY outcome
Timeframe: 12 months post HSCTPopulation: Nine subjects received a single dose of ATIR101 and 6 subjects received a double dose of ATIR101.
Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first
Outcome measures
| Measure |
ATIR101
n=15 Participants
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
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|---|---|
|
GVHD-free, Relapse-free Survival (GRFS)
Single dose, Kaplan-Meier estimates of GRFS
|
55.6 Percentage of participants
Interval 20.4 to 80.5
|
|
GVHD-free, Relapse-free Survival (GRFS)
Double dose, Kaplan-Meier estimates of GRFS
|
16.7 Percentage of participants
Interval 0.8 to 51.7
|
Adverse Events
ATIR101
Serious events: 7 serious events
Other events: 8 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
ATIR101
n=15 participants at risk
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
|
|---|---|
|
Immune system disorders
Acute graft-versus-host disease (GVHD)
|
33.3%
5/15 • The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
|
|
Immune system disorders
Chronic GVHD
|
13.3%
2/15 • The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
|
Other adverse events
| Measure |
ATIR101
n=15 participants at risk
ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).
Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
* Total Body Irradiation (TBI) regime
* Non-TBI regime
(See below for details)
TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
* Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
* Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
* Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
* ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
|
|---|---|
|
Immune system disorders
Acute GVHD
|
46.7%
7/15 • The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
|
|
Immune system disorders
Chronic GVHD
|
13.3%
2/15 • The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
|
|
Investigations
Cytomegalovirus (CMV) positive
|
6.7%
1/15 • The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
|
Additional Information
Andrew Sandler, MD / Chief Medical Officer
Kiadis Pharma Netherlands B.V.
Phone: +1 206 779 9213
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place